HIV-1 uncoating is a poorly understood field and strengthening the idea behind this mechanism will add a strong base to the viral life cycle and interesting targets for antiviral therapy. Our previous work on the role of microtubules during HIV-1 uncoating has provided valuable information to the field of trafficking and HIV-1 uncoating. Our preliminary work supports a strong dependency of several microtubule associated proteins (MAPs) during HIV-1 uncoating and involvement of a variety of other host factors in this process. With this, we propose three specific aims to explore the role of these MAPs during HIV-1 uncoating. Our first aim would be to decipher a mechanism by which these MAPs control viral uncoating. In the second aim, we would further characterize how the viral core trafficking is controlled by these MAPs and in the last aim, we would define the direct interactions between MAPs and the viral core which contribute to HIV-1 uncoating and trafficking. Our expertise and collaborations would help achieve these specific aims and show how the microtubule trafficking machinery plays an important role during HIV-1 uncoating. Findings from these proposed aims will provide critical understanding to the molecular interactions which drive HIV-1 uncoating and trafficking and would help identify better candidates for future antiviral therapy.